SA98190059B1 - Tetrahydropyrido compounds - Google Patents

Abstract

1. Technical Result Increase in enteral efficiency and protective action of gastroenteric tract. 2. Essence Compounds of formula (I) (meanings R1, R2, R3, R4, R6, R7, R4a, R4b, R5a and R5b are given in the description) and medicine on their basis. 3. Field of Application Medicine.

Description

Y

tetrahydropyrido compounds Full description TECHNICAL BACKGROUND: The invention relates to new compounds used in the pharmaceutical industry as active compounds .medicaments for the production of active compounds [=O] US Patent No. £80080 describes compounds Imidazos containing various ring systems tricyclic imidazo[1,2-a]pyridine Basic tricyclic pyridine suitable imidazopyridine integrated on the structure of imidazo-pyridine various ring systems .peptic ulcer disorders peptide da j3 to treat Disorders General description of the invention:] The invention relates to compounds of the formula

R3 = R2

Rab—Y"N

RaNH0

R&b =

ry

Where 0 represents alkyl-N-Ren and 1-40-1 hydroxy-1-4C-alkyl or hydroxy-alkyl-Pt-Ren 1-4C-alkyl represents Alkyl-.J0-© 2 R4b and Rda atoms, and one of the two alternatives represents a chalogen or a hydrogen halogen, representing a 3-hydroxyl hydrogen atom, and the other substituent represents a hydrogen atom, hydrogen of alkoxy-©-0-alkoxy<-- ‎ ¢1-4C-alkoxy Alkroxy-Hi-N ¢hydroxyl 10m

. 1-4C-alkoxy-1-4C-alkoxy, i.e. the alkene, we are carbonyloxy, 1-4C-alkylcarbonyloxy, or where R42 J— Sy and Lae R4b are a coxygen oxygen atom, and includes a al of the two substituents, RSa And 856 hydrogen atoms. alkoxy or C=Ci—J— SI carbonyloxy “1-4C-alkylcarbonyloxy” or dua 258 and 8560 together form an oxygen atom 0 or where one of the substituents 848 and 845 represents on the one hand and one of the substituents E85 and 8506 on the other second in each Ala 0 30 hydrogen chydrogen and the other two substitutes in each case Lae are redical methylenedioxy (0-:0-011-) or ethylenedioxy (-O -CH,-CH,-0-) ethylenedioxy where radicals “Rda” do not represent RSa and RSb at the same time a hydrogen atom chydrogen 6 represents a hydrogen atom chydrogen alkyl halogen - n (1-4C-alkyl C=C oS SI ¢1-4C-alkoxy C=C nS SI Vo carbonyl amino “1-4C-alkoxycarbonylamino alkoxy-,0--alkoxy-,0- 0: carbonyl amino 1-4C-alkoxy-1-4C-alkoxycarbonylamino or PN trifluoromethyl 7 represents a hydrogen atom chydrogen halogen “alkyl-N- 1-4C-alkyl or ¢”1-4C-alkoxy C= Cy nS SN and salts of these compounds. 1 and 1-4C-alkyl C=C, ISH has straight-chain or branched alkyl radicals containing from 1 to ; 8500 AH carbon atoms. Examples that can be mentioned include cbutyl root cisobutyl root sec-butyl root tertiary-butyl ctert-butyl root cisopropyl ethyl root and methyl zata root. Preferably the root of the instance to feed. Yo represents hydroxy-alkyl-yen hydroxy-1-4C-alkyl alkyl radicals-,0- 1-4C-alkyl mentioned above that carry a substituent from the hydroxyl group, examples that can be mentioned include the hydroxymethyl radical hydroxymethyl 7-hydroxy radical Y «Ao

Jia “-Hydroxy-propyl M300<H:3-70. preferably das 2-hydroxyethyl J -hydroxymethyl hydroxymethyl or chlorine <bromine in the invention bromine halogen meaning halogen.fluorine roots contain; In addition to the oxygen atom, 1-4C-alkoxy, which represents the alkoxy-,©7-© to; 1 atoms with a straight or branched chain containing from an alkyl an alkyl oxygen radical a cbutoxy radical mentioned by the butoxy radical Sa and the amazes which include carbon Nth-butoxy carbon Aa a t-butoxy radical " “Mendet H”; cisobutoxy, isobutoxy, preferably isopropoxy root (: 0m80m;_ cert-butoxy .methoxy root and ethoxy 6 roots DA 1-4C-alkoxy -1-4C-alkoxy Wimit the alkoxy-,©-©- Alkoxy-N-0©

CC SSI from the aforementioned Say root bearing 1-4C-alkoxy alkoxy-b©-,© Ss which can be mentioned as another 7-(methoxy) AB root. These include 1-4C-alkoxy 2-(ethoxy)ethoxy and '-(ethoxy)ethoxy (CH;-O-CH,-CH,-0) 2-(methoxy)ethoxy (CH;-CH,-). 0-CH,-CH,-0) 0 carbonyloxy group 1-4C-alkylcarbonyloxy carbonyloxy C=C JS and represents the above mentioned. An example includes 1-4C-alkyl C=C SY to which a carbonyloxy radical is attached (CH; CO-0-) acetoxy. It can be mentioned that the carbonyl radical has a carbonyl group of 1-4C-alkoxycarbonyl and represents the alkoxy-, 0-© carbonyl mentioned above. Examples to which the 1-4C-alkoxy is attached include an alkoxy radical,©7,© “©” and an ethoxy radical (CH,0-C(0)-) methoxycarbonyl His la S30 (Sa - (CH;CH,0-C(O)-) ethoxycarbonyl carbonyl amino amino radical 1-4C-alkoxycarbonylamino sind carbonyl Ci Cy mS 5S) and represents the above-mentioned 1-4C-alkoxycarbonyl Carbonyl C= Cy oS SHY carries a substituent of one of the roots and the ethoxycarbonylamino root which can be mentioned ethoxycarbonylamino root BY and includes Ye .methoxycarbonylamino methoxycarbonylamino 01m

The alkoxy-0-0-loxy-n-0-carbonyl 1-4C-alkoxy-1-4C-alkoxycarbonyl represents a carbonyl group to which an alkoxy radical is attached -,©-.©-alkoxy-,©-© 14C-alkoxy-1-4C-alkoxy mentioned above. Examples that can be cited include the 7-(methoxy) enoxycarbonyl radical (CH;-0-CH,CH,-0-CO-) ° and the Y -(ethoxy)ethoxycryoyl radical 2-(ethoxy)ethoxycarbonyl .(CH;CH,-0-CH,CH,-0-CO-) alkoxy-1-4C-alkoxycarbonylamino amino carries a substituent from one of the C=C nS SIC = C= nS SY carbonyl 1-4C-alkoxy-1-4C-alkoxycarbonyl radicals mentioned 0 above. bY) that can be mentioned include the 2-(methoxy)ethoxycarbonylamino radical and the 2-(ethoxy)ethoxycarbonylamino radical and include the appropriate salts of the compounds of formula 1 - Depending on substitution 501500008 - in particular every 1 for salts in addition to acid addition salts (aes). It can be mentioned in particular the 10 pharmacologically tolerable salts of inorganic acids and organic acids used These suitable salts include salts in addition to water-soluble and water-insoluble ALE with acids such as chydrochloric acid, chydrobromic acid, or phosphoric acid. phosphoric acid nitric acid 000 sulfuric acid acetic acid acid e citric acid 7-gluconic acid D-gluconic acid benzoic acid 7-(; - Hydroxybenzoyl) 2-(4-hydroxybenzoylbenzoic acid) butyric acid (butyric acid) sulfosalicylic acid (csulfosalicylic acid) Halle (maleic acid) lauric acid dauric acid malic acid fumaric acid Yo Lighter fumaric succinic acid oxalic acid coxalic acid tartaric acid acid Amabha aes cembonic acid li gl aes stearic acid toluenesulfonic acid ctoluenesulfonic acid methanesulfonic acid acid or an acid

'-hydroxy-7-naphthoic acid (3-hydroxy-2-naphthoic acid) where acids are used in the preparation of the salt - depending on the type of acid used, whether mono- or polybasic acid, and depending on the desired salt - in an amount Equimolar quantitative ratio or a different proportion thereof Joma ° pharmacologically intolerable salts that can be initially obtained as Je process products for example in the preparation of compounds according to the invention on the scale of ela into permissible salts (lie) by processes known to the person skilled in the art. According to the knowledge of the expert, the compounds and salts of the invention, Sia when separated in crystalline form, may contain varying amounts of solvent. Therefore, the invention includes in its scope All the solvates and in particular all the hydrates of the compounds in formula 1, as well as all the solvates and in particular all the hydrates of the salts of the compounds in formula 1. The compounds in formula 1 contain three chiral centers. All stereoisomers (Auld) that can be realized with any desired mixing ratio with each other; Including the ¢pure enantiomers which are the preferred material of the invention. And if one of the substituents 848 and 846 on the one hand and one of the substituents 858 and RSD on the other hand form together a methylenedioxy radical or a cethylenedioxy radical | 0, it is preferable that the two substituents whose OUT Ky methylenedioxy radical or ethylenedioxy radical are adjacent to each other. Compounds that should be mentioned include those with the formula [©, where 1 represents alkyl-N-Ren «1-4C-alkyl R2 represents alkyl-©- 0 1-4C-alkyl or hydroxy alkyl-N-0 chydroxy-1-4C-alkyl Yo 83 represents a hydrogen atom v, the other substitute represents a hydrogen atom, a hydrogen atom Rab, and one of the two substitutes represents 1848 and

JT Kay or where 1-4C-alkoxy Ci—Cy— nS or hydroxyl hydrogen coxygen together represents an oxygen atom R4b M4 and the other substitute represents a hydrogen atom RSb represents One of the two alternatives is 1858 and

JT <i Cus << hah1-40©5” or C=C oS SI or hydroxyl hydroxyl hydrogen © coxygen together an oxygen atom R5b and 58 hydrogen and 856 at the same time a hydrogen atom RSa 845 radicals do not represent M84 Cus and trifluoromethyl or trifluoromethyl halogen, a hydrogen halogen 6 chalogen or a hydrogen 7 chalogin and salts of these compounds. 0 : 1* An embodiment of the invention should be mentioned includes compounds of the formula YM R2 3 0 SLA 1 © AH 81

Rd YY N Al 0) L’ A M 87 where ¢ 1-4C-alkyl represents the alkyl- R1 chydroxy-1-4C-alkyl i.e. hydroxy alkyl-0-n 1-4Calkyl C,—Cm dS is 2 0 hydrogen is a hydrogen atom R3 The other substituent is a hydrogen atom Rab One of the substituents is 842 and ¢1-4C-alkoxy or alkoxy -,0-6 hydroxyl hydroxyl hydrogen The other substituent represents a hydrogen atom and 855 hydrogen atoms RSa One of the two substituents represents 1-4C-alkoxy C=C oS SJ or hydroxyl hydroxyl ¢hydrogen 0 hydrogen and 1850 at the same time a hydrogen atom 1858 “R4b radicals P848; Jud no Cus C01

A

or trifluoromethyl halogen hydrogen representing a hydrogen atom 6 and trifluoromethyl chalogen or hydrogen halogen representing a hydrogen atom 7 and salts of these compounds. An embodiment of the invention that should be specifically mentioned includes compounds of the formula * a; where ; (1-4C-alkyl R1 <hydroxymethyl Jie or hydroxy 1-4C-alkyl C—C— JS ha 2 hydrogen R3 chydrogen Réa ¢1 -4C-alkoxy or alkoxy-0-0 hydroxyl represents hydroxyl 845 0

C= Cy oS 5S or hydroxyl hydroxyl hydrogen representing 53 hydrogen 8 ¢«1-4C-alkoxy hydrogen representing 0 hydrogen atom and trifluoromethyl or trifluoromethyl halogen (pa dla hydrogen representing A hydrogen atom 6 chalogen or a halogen hydrogen A hydrogen atom Jig 87 Vo and the salts of these compounds. For 1-40 anoleum C,—C,— Represents alkyl R1 Represents alkyl-E- 1-40 2 chydrogen represents a hydrogen atom 83 | 0 chydrogen represents a hydrogen atom Ra hydroxyl represents a hydroxyl R4b hydroxy! represents a hydroxyl RSa <hydrogen represents a hydrogen atom 506 methyl gold or thirty halogen 3) hydrogen representing 50 hydrogens R6 Ye and trifluoromethyl chalogen or halogen hydrogen atom of hydrogen Jia 7

And the salts of these compounds. For the invention, Lady, the following typical compounds can be mentioned, IF, and with the help of the following general formula: 3,2 ha

Xp

R4a pe 1 p. Ri rd Mo

Rig, NH5

R3b Dir Atan ref “Rk

ry

°

R7 R6 R5b cc R4a 3 R2 RI

H H H H 0 H CH; CH,

H H H H OH H H CH; CH,

H 2-Cl H H 0 H CH, CH;

H 2-Cl H H OH H H CH; CH; 6-Cl 2-Cl H H 0 H CH, CH, 6-Cl 2-Cl H H OH H H CH; CH;

H H H H OCH, H H CH; CH;

H H H H OCH; H H CH; CH;

H2-CF; H H 0 H CHCH;

H2-CF; H H OH H H CH, CH,

H H H OH 0 H CH; CH;

H H H OH OH H H CH; CH;

H H H H 0 6-BrCH; CH;

H H H H OH H 6-BrCH; CH,

H H H H OH H 6-ClCH; CH;

Y «Ao

Yo

R7 R6 R5b RS5a R4b R4a R3 R2 R1

H H H OH OH H 6ClCH; CH;

H 2-Cl H OH OH H H CH; CH, 6-Cl 2-Cl H OH OH H H CH; CH,

H 4-Cl H OH OH H H CH; CH,

H2-CF; H OH OH H H CH, CH, 6-CH; 2-NHCO-OCH; H OH OH H H CH; CH, 6-CH; 2-NHCO-OCH, OCH; H OH OH H H CH; CH;

H H H H 0 H CHOH CH;

H H H H OH H H CHOHCHCH,

H 2-Cl H H 0 H CHOH CH;

H 2-Cl H H OH H H CHOH CH, 6-0 2-01 H H 0 H CHOH CH; 6-Cl 2-01 H H OH H H CHOH CH,

H H H H OCH; H H CHOH CH;

H H H H OCH; H H CHOH CH;

H2-05H H0HCH,OHCH,

H2-CF; H H OH H H CHOH CH;

H H H OH 0 H CH,OHCH;

H H H OH OH H H CHOHCHCH,

H H H H 0 6-BrCH,OHCH;

H H H H OH H 6BrCH,0HCH;

H H H H OH H Hm CHOH CH;

H H H OH OH H Hm CHOH CH,

H 2-Cl H OH OH H H CH,OH CH, 6-Cl 2-Cl H OH OH H H CHOH CH;

H 4-Cl H OH OH H H CHOH CH, \ «Ao

11

R7 R6 R5b RSa Rdb Rd4a R3 R2 RI

H2-CF; H OH OH H H CHOH CH; 6-CH 2-NHCO-OCH; H OH OH H H CHOH CH; 6-CH; 2-NHCO-OC,H-OCH; H OH OH H H CH OH CH;

Cn (oxygen) and salts of the compounds listed in Table 1; the symbol “0” (oxygen atom 7-0x0 and SCA-17) denotes compound 1 roots 1848 and 845 in the table of the invention as described for example in Lay Preparation of compounds (Sey and so on) from appropriate precursors.f the following examples; or using similar process steps 0 Prepare them in a manner similar to the method for preparing Sey (Sey) and known primary compounds or compounds. (R5a/ RSb (see R4a/Rdb) A and 1 and depending on the substitution pattern in the two positions [-7 0] of Ted +-amino imidazo compounds, compounds can be prepared according to the invention containing a protective group at the nitrogen atom 8-aminoimidazo[1,2-alpyridine] Prepared by a known method (see eg the well-known patent or nitrogen Say and collaborators in Kaminski for ela or what A= 799 4976 European Patent No. pp. 847-4975 9465 1 CE) according to the following reaction schemes: “YA vol. (J. Med.Chem. das 1: Scheme B)

VY

Die 3 2 A >

Fa Ghala HC A Al Rah he MHP

NMP! co i)

So 7g x 82mm R3 +A

NE nor Oa LD 84 le] en, J 0 Nr WNHPw Sa A 0 rE Re - 3 R7

R3 Fe R3_{i gat CI

Ox SA HO Ay ny Lee 7 Ah

I ohm one and 8-aminoimidazo[1,2-ajpyridine pyridine]-1 1-aminoimidazo is reacted and contains a protective group at the nitrogen atom 17 deprotonated at position B »1 In this scheme and in the following schemes, the nitrogen group Ji) is represented. The cinnamaldehyde is oxidized with regular pivaloyl cinnamaldehyde, preferably the bivaloyl group 481, © (manganese dioxide using manganese dioxide Mia) Y 4 addition product Addition product under conditions 0 (hydrogen peroxide using hydrogen peroxide ia) and then epoxied with basic and then highly acidic; removal of the protective group and closure of the sand ring as desired; keto and the next reduction step can be performed Keto Kit .ring closure .sodium borohydride Nia using 01 chart ?: 1 dl

for R2 R2 R3 / 83 ay 21 81 arla NH ht x NHPW os RE ! 8 x R7 87 R2 m a eC 0 R7 Instead of the epoxidation step according to Scheme 1; the protective group is removed and the ring closed under highly acidic conditions. The next reduction step is carried out for the calcohol as desired; using sodium borohydride Ao

VE

Diagram?: pi f io wf) sama o { 83 / NT a mhna

ROE. NHPv

NHPiv 0

R2 R2 83 83

CAR Can 0 Thief HO, SP — NH Hm NH

H? HO : b b

R7 87 centantioselective synthesis The above scheme represents an example of selective synthesis of imidazo[1,2-a]pyridine [FY OV] The same imidazo compounds were used as starting materials as in The diane nitrogen outline on a protective group at this nitrogen atom °e in imidazo[1,2-a]pyridine pyridine [=v 1] is produced by the reaction of imidazo compounds

La pure dioxolanes with deprotonated form deprotonated form Can be converted into a ring in condensation product Y enantiomerically pure under highly acidic conditions with removal of protective groups. Subsequent reduction of group (1) (see also chart) results in sodium borohydride using sodium borohydride keto 0 7960 in excess of enantiomeric purity, the final product shown as pristine purity.

V + mi

Yo : 4 Chart 3 2m on Ra Di

Neh CO, Eh, [= pi I + Rss LAB 8. L eR Ham. ml 5

NH : = 5 RSs + I J rds k F RE 7 1 I 8 but So and RE 7

RY RZ

SE

Os Jn

Keo Jo MH

RS

Free RE 7 imidazo [1, 7-] pyridine dA Starting from compounds, compounds bearing the mentioned coded substituents 8-aminoimidazo[1,2-a]pyridine alkylating 2 are obtained Using alkylation agents either by alkylation of the 8-amino on the 8-amino group ©

R8b and hydrogen represent 53 hydrogen (8 Sia) suitable substituents bearing 15 substituents using reductive alkylations or reductive alkylation steps (halogen 3,0 fia together © (atom R8b and R8a appropriately carry substituents [ketones form sodium borohydride ketone compounds sie such as reductants with the help of reducing agents [(oxygen) and subject these resulting compounds to ring closure under sodium cyanoborohydride catalytic conditions 0 Cyclic kentones can be converted to produce base or acid catalysis chemical transformations on their part to the desired compounds using chemical conversion methods and ?). Convenience (see for example the two schematics and then cyclization before ring formation (aldehyde) (aldehyde production stage Y or COR group can transform from 1 _ at the hydroxy position bearing substituents of hydroxy derivatives derivatives yo .oxidation/reduction in terms of their respective redox-appropriate target compounds: 0 Scheme 1 dl

a a a a m a m a m a k Ns NH, ~ or Q 4 eo AL 9 or ' PAX, Sa 2 b RICA, a 8 < N 2 N JR b Totem oy xz T RO Nk l or lbr ° bb wm Rs RY NY -. 3. AL RI OD NF A Baal | 3 0 Bisr Hob > ‎HO, . l > J N d Ho — wd HO a y ed n a - 17 Rs in a variation of the above process in the diagram; Where 852 and H=R8a (hydrogen atom) and each of R5b and R8b with it (oxygen atom ' Jel tye) first compound 8-amino imidazo [1 7-a] Pyridine is 8-aminoimidazo[1,2-a]pyridine with an epoxycinnamic acid ester derivative with a regioselective epoxide opening of 0. A ring of products is formed under aprotonable base conditions. (—)oprotic basic conditions Alternatively, the mixture can be hydrolyzed and a ring of free carboxylic acid is formed under acidic conditions 0 (2) conditions | 0 In either case, the keto group can be reduced Subsequently to alcohol, alcohol (0) » as shown in the diagram oY mfla using sodium borohydride. AO

VY epoxycinnamaldehyde with epoxycinnamaldehyde derivatives 8-aminoimidazo[1,2-aJpyridine] buffered (b) the ring of products can be closed under acidic conditions after removal of the acetal functional group to the protective aldehyde ester (9). Reduction of the acetal ester group and formation of a ring in acidic conditions (2-). Both the reduction of the aldehyde group can be selectively carried out with the aldehyde functional and the ring closure in the keto aldehyde production stage so that the synthesis of Enantioselectivity when using the corresponding enantioselectivity epoxy derivatives. 1 + AO

m chart: eH 0 and oH L, Sy - free LT — Ww nr ph ny 8 #! 9 p. v 7 7 i ¥ bm pr Ae 7 pg Re” er | wd R2 83 R2 83 a NT 1 m NH ¥ Ty Nyt Ph 7 C3 0 2 0 C3 7 87 RS Re R3 2 R3 nz 81 dr 81 atmosphere Bit Qa, Et Og, MD - NH mr PC I NH Pr RE = total a protective ic RS 8 = easy-to-remove group » - Bel NR, OR 3 5, Halo Gene 86 and Mah 6: etc. In another variant of the process shown in the diagram above, the selective synthesis of oo is shown in such a way that the Wh derivative of dihydroxycinnamic acid is in the benzyl group position, either directly or After the incorporation of a protective group on the second hydroxyl group. dels Tag The products obtained in this way with the compound -aminoimidazo [A] 1-a]pyridine -8-aminoimidazo[1,2-a]pyridine and then the Nie ring is closed under basic conditions basic conditions and the next downsampling step is performed; 0 as desired; in a manner similar to that shown in the diagram?. Scheme 7: A 101 x 2g NHY 3 COOR H + MILES > > Yb X 87 : {Pd) 3 3c : 2g RZ

SE A 1 1g ALA XN 0 moiety Ba 52g A Ba 53g RSD [5b c g RY 8-haloimidazo reaction 8-haloimidazo[1,2-a]pyridine (pu) [i-Y A] =X) a halogen atom with B-phenyl-B-amino acids bearing oo suitably substituents with a heavy metal catalysis procedure metal catalysis (Pd is preferred for the production of 65 amines bearing substituents that convert from their side to a ring according to the scheme of and instead of the group 0008#; Load (Say) the use of the aldehyde group LS) aldehyde mentioned in the scheme; (Gila In the form of acetal, as desired. Y represents a hydrogen atom or a protective group that can be removed after the ring is closed.

Chart (A 1 COOR um = raed R7 (1 1 TNT TR y SR —_— oH o ROCC Pe 2 : Jum Berga 87 : R2 R3 R2 Rs N + A oo LI = SS TT Opa NH NH HO HO HO Re" Re] I x b R7 a L 7 NTN 81 por NH hep HO wd 87 fey of imidazole which is known or can be prepared by a method italicized 6 el al prefers to close the ring (and optionally by making a protection for the hydroxy group in The presence of an enamine structure (in the state of equilibrium) and after the fusion of the double bond by oxidation; the reduction step of the keto group to the alcohol can occur as shown in Scheme 1 and in the above schemes; » represents an alkyl -©-,© 1Walm©1-40. In the ester groups mentioned but not limited to (-COOR) or 0:8), there may be another easy-to-remove group in place of the root OR or There may also be another group that can be used as far as its function is concerned in place of the ester group A1

Ji 255/858. or 840/848. Cua | The compounds can be prepared with the formula Alkruxi-and-wasam 140 Alkruxi-0-H-l-l-carboxy-1-4C-alkylcarbonyloxy | carbonyl oxy C—C—Jd I see 1-4C-alkoxy-1-4C-alkoxy the usual procedures of a person skilled in the technique (eg Jie with ordinary derivational procedures;

Gus from the corresponding compounds “(acylation or acylation alkylation by alkylation 0 hydroxyl hydroxyl de gana or 55/85 representing R4b/R4a

CC dS represents hydroxy R2 and compounds of formula 1 can be produced where from esters A to 1 or corresponding primary compounds in the schemes of hydroxy-1-4C-alkyl for example sodium borohydride “Jl AVL alia) aldehydes and aldehydes 5 in the usual manner ¢lithium aluminum hydride or lithium aluminum hydride sodium borohydride | 0 Ae) Patent International No. 181449/15 can be made. According to sel sok ki) simultaneously with hydroxy-1-4C-alkyl reductase to produce the hydroxy-alkyl group-©-©, they form Rab and Raa) 17, particularly in the A site at the site keto is the reduction of the keto group (oxygen an oxygen atom las) and the materials are separated according to the invention and purified in a method known by itself, for example by removing the resulting solvent in a suitable solvent or subjecting it to a residue by distillation in vacuum and recrystallizing the ore on Column chromatography Column chromatography Regular Jie purification Purification methods are suitable. methyl chloride Jia «chlorinated hydrocarbon Low molecular weight aliphatic alcohol or aliphatic alcohol cchloroform containing the desired acid or solvent (isopropanol cethanol Js) The salts are obtained by filtration or re-dean to which the desired acid is added later. Precipitation or precipitation without the use of a solvent for the added salt or by evaporation of the solvent. Compounds can be acidification or alkalization, transforming the salts obtained by vo alkylation. The shot, which in turn can be converted into salts. In this way, salts other than 10 M can be converted

YY

into pharmacologically intolerable salts and in particular pure enantiomers. The pure enantiomers to which the invention relates may be obtained preferably; In a style familiar to someone experienced with IF of the form fF by a priori selective synthesis (see eg; technical diagram She; oe on columns chromatographic separation by chromatographic separation of d:uh; Auxiliary non-chiral reaction sepatating columns, removing the diastereomers auxiliary group, then separating the chiral auxiliary reagents “chiral acids” uh, by forming a salt using non-chiral auxiliary group acids, then separating the salts and releasing the desired compound from the salt or by (fractional) crystallization in a suitable solvent. (fractional) crystallization of process intermediates The invention further relates to processes and intermediates in And) and in particular those intermediates of the dled process described in the drawings can be separated before the ring formation step. apparent in a similar way or in a style familiar to a person skilled in the art using standard processing techniques. When measuring the mass spectrum the following symbols are used: “Rn-m denotes nuclear magnetic resonance; delta to denote the difference; So to indicate a single spectrum, on the coupling coefficient; Jad shook the g to indicate a double spectrum; p to denote a multiple spectrum; c Lid to denote Hertz ad End Products [VO]Hydro imidazo [0 7-H] Trans-01 A Methyl-4-Phenyl-E SEY Ye (V) Naphtheridinone 2,3 -dimethyl-9-phenyl-7.8.9,10-tetrahydroimidazo[ 1,2-1,7]naphthyridin-7-one 01m yy -ska-1-lenf-©(-7-litham) SEY 17 gram (0) A solution of 6.0 g was treated with 2,3-dimethyl-7-(3-phenyl-1-oxo0- ?-a]pyridine OO] "-propenyl)-/-bivaloyl amino imidazo dioxane 0 mL dioxane in 2-propenyl)-8-pivaloylaminoimidazo[1,2-a]pyridine heated with rewind for ¢ 3S ye hydrochloric acid mL of Yr hydrochloric acid — hours and temperature controlled Its acidity was reduced to 7 using sodium hydroxide solution Ao ml of 50 N with cooling and extracted three times with 1 of its concentration sodium hydroxide and dried over celal carbonate and washed the extracts after mixing them with ethyl acetate and concentrated until and the viscous oil potassium carbonate ethyl acetate was eluted by lysate using a mixture of silica gel remaining on silica gel 1.7 g of eluent as lysate mix 1: 1 in the proportion of petroleum ether and petroleum ether 0 from 18 H 6 C. melting point The compound named in the title whose melting point [7=Y ON] is 9; 10-tetrahydrimidazo A Vode JET -(7”-chlorophenyl)-” LY (V) naphthyridinone [VO] 9-(2-chlorophenyl)-2,3-dimethyl-7,8,9,10- tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

Ar contains the compound named in the title whose melting point is Ga' a vo

ET Yd leolafib-4-[linipurb-7-osca-1-(linfurolic-7)(-7[-7”im_from 7-[3-(2-chlorophenyl)-1-oxo0-2-propenyl]- 8-pivaloylamino- pyridine [i-¥ A] methyl imidazo (modified 1 in the same manner as compound example 2 3-dimethylimidazo[1,2-a]pyridine (vy = z wy methyl-a) 4 9 10-tetrahydrimidazo JET>-dichlorophenyl)-; 2,3-dimethyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7- one

AYEA-YEA Get the name in the title whose melting point ranges from

AE Y= gid leolafib-4-[liniporb-7-osca-1-)linfurolac ET TY.”from 7-[3-(2,6-dichlorophenyl)-1-ox0-2-propenyl]- 8- Pyridine [I=Y imidazo b J a

Ye 1 In the same way as the example compound, pivaloylamino-2,3-dimethylimidazo[ 1,2-a]pyridine 4 1 (production rate - hydroimidazo trans-01) A Vode SUEY 9-(7-tri) fluoromethylphenyl)-7; Lg (7) naphthyridinone [V[1 7-h] 0] 7-one

TIAL contains the compound named in the title whose melting point ranges from Ja Ca

X= from 7-[7-(7-trifluoromethylphenyl)-1-exo-7-propenyl]-8-bivaloyl amino 2) AO 7-[3-(2-trifluoromethylphenyl)-1-0x0-2 - Pyridine [A-1 AV] methyl imidazo SY in the same manner as propenyl]-8-pivaloylamino-2,3-dimethylimidazo| 1 ,2-a]pyridine 0 (6) = z (modified 1 example compound methyl-4-phenyl-/a 4.10-tetrahydrimidazo SEY;?-iscordia-17 Le naphthyridine ‎ [VY A] [=X] 7-hydroxy-2,3-dimethyl-9-phenyl-7.8,9.10-tetrahydroimidazo[ 1,2-h][1,7]naphthyridine methyl-9-phenyl-ate K SEY CY 1 g of supspension treated with VO 2,3-dimethyl-9-(V)nephthyridine [VO] [2=Y O] hydroimidazo trans-0 ml of YO methanol in phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one in milligram (mg) borohydride at room temperature b. 456 mg methanol in small batches The resulting striking solution was stirred to sodium borohydride sodium percipitate by vacuum filtration for 2 hours and then diluted with ice water The precipitate was removed © and washed with a small amount of 7-propanol 0′ Hm: M2 cold, produced 8060 mg of the compound named M. 701-717 in the title whose melting point ranges from Hydro Trans-01 A A Vode JECT 7-Iscordia-17-(Linfurulic-7)-4 LY Naphthyridine [VO] [7-8 Np aed 9-(2-chlorophenyl)-7-hydroxy-2,3-dimethyl-7,8.9,10-tetrahydroimidazo[ 1,2- vo h][1,7]naphthyridine 01 mM ,

\ dia Ta on the named compound in the title whose melting point ranges from -101 "0 C of 4-(7-chlorophenyl)-7Vd fe SUEY 8 4 10-tetrahydrimidazo [V oY ] [—Y AN] naphthyridinone 9-(2-chlorophenyl)-2,3-dimethyl-7,8,9,10- (V) tetrahydroimidazo[1,2-h][1,7]naphthyridin -7-one in the same manner as compound example #e (production rate 0-(VY HET (5 LY chlorophenyl)-1-hydroxy-; *-dimethyl-la 48 4 10-tetra) hydroimidazo[0;[VN[=F naphthyridine 9-(2,6-dichlorophenyl)-7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydroimidazo[1,2-h] [1.7]- naphthyridine Ve solution on the named compound in the title whose melting point ranges from ep YoY 00 4-(7; JET chlorophenyl)-; Vie SEY 8 4 10-tetrahydro imidazo “0[ [—Y A] 7] naphthyridinone 9-(2,6-dichlorophenyl)-2,3-dimethyl- (V) 7,8.9,10-tetrahydroimidazo[ 1,2-h][ 1,7]naphthyridin-7-one in the same manner as the example compound O (production rate-7/).A ve 4-(7-trifluoromethylphenyl)-/1-hydroxy-; SUEY methyl -/A8 4;10-tetrahydroimidazo [0;7-h] [VO] naphthyridine 9-(2-trifluoromethylphenyl)-7-hydroxy-2,3-dimethyl-7.8,9,10-tetrahydroimidazo [1,2-h][1,7]- naphthyridine obtained the compound named in the title with a melting point range of £0” © L of 4-(7-trifluoromethylphenyl)-7; SUEY instance-7; 8 9 10-tetrahydr imidazo A] ?-h] [VO] naphtheridinone 9-(2-trifluoromethylphenyl)-2,3-dimethyl- (V) 7,8,9,10- tetrahydroimidazo[1,2-h][1,7]-naphthyridin-7-one was prepared in the same way as the example compound o (modified (7VY = z wy) 4.4-hydroxy-7;7-dimethyl) was prepared. -1-phenyl-/a;A4;10-tetrahydrimidazole ve 1[7-h]]0] naphthyridinone (V) 8-hydroxy-2,3-dimethyl-9-phenyl- 7.8.9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

A solution of 500 mg of SEY OY was treated with methyl-7-(7;7-epoxy-1-oxo-“-phenylpropyl)-”+-bivaloyl sud imidazo [OV]7-a]pyridine 2,3-dimethyl-7-(2,3-epoxy-1- oxo-3-phenylpropyl)-8-pivaloylaminoimidazo[ 1,2-2] 110106 in ¾ mL ethanol Jol dry, stirred vigorously with 40 mg of lithium hydroxide and after stirring 0 at room temperature for 2 hours, cooled to 0°C in an ice bath, the precipitated crystals were removed by vacuum filtration and washed with a small amount of cold ethanol, and after drying in vacuum The solid was added to ¾ ml of sulfuric acid concentration of 7950 at room temperature and the mixture was stirred for one hour.Then it was replaced with a cooled sodium hydroxide solution of concentration of 740 with ice cooling.The precipitate, Ve, was removed. By filtration in this process and dried in vacuo, it produced £0 mg of the named compound in the title, whose melting point ranged from 74-777 C. 0 AA EEA hydroxy-e “-di-methyl-4-phenyl-/ ely) eA hydroimidazo 01 7-h] [V AT naphthyridine 7,8-dihydroxy-2,3-dimethyl-9-phenyl-7.8.9.10-tetrahydroimidazo[1,2-h][1,7]naphthyridine vo suspended 001 mg of 48-hydroxy-7; JUST methyl-4-phenyl-a p34-01 tetrahydrimidazo [OV] 7-H] [V OV] naphthyridine 8-hydroxy-2,3-dimethyl-9-phenyl- (V) 1,7]-naphthyridin-7-one |[i-1,2 7,8,9,10-tetrahydroimidazo] in Jo VO methanol and the suspension was treated with Yoo mg of sodium borohydride by adding it in batches at room temperature with stirring. After stirring for two hours, pour the © mixture into 100 ml of ice water. The precipitate was removed by filtration, dried in vacuo for a short time, and recrystallized in a small amount of ?-propanol 1o00oC-8 «8, producing pale 90800 from the named compound in the title whose melting point ranges from 197-1691oC. AA Voda aS gaa Adie SUEY; 7-)G4 RA) 10- Tetrahydro

(Y) naphthyridinone [VN [=F OV] imidazo (8R.9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7,8.9,10-tetrahydroimidazo[ 1,2- Yo h] [1.7] naphthyridin-7-on

01.8 g YE millimol (mmol) of 7 methyl-7-SEY (Y=(RY 57)[0-7-isopropyllidene-7-phenyl-1) was added -propanone (1)-1-yl]-+-bivaloyl amino imidazo “V] 1-a] pyridine 2,3-dimethyl-7-[(2S,3R)-2,3-O -isopropylidene-3-phenylpropan- ‎Rectus =R) 1-on-1-yl]-8-pivaloylaminoimidazo[ 1,2-a]pyridine Any compound that deflects light © clockwise» 5- Sinister any compound Deflects the light counterclockwise) The initial excess quantity > 790 by HPLC analysis using a Daicel Chiralcel column to 0 © ml of sulfuric acid of 770 With cooling with ice within minutes.Within this period of time it forms a Blan that turns into an orange solution after +© minutes.After the completion of the addition Azaril 0 ice bath and the mixture is stirred at room temperature.After 50 hours a solution is added The reaction was to mf Bo water and dichloromethane was added and the pH of the mixture was adjusted to A using a 1 M sodium hydroxide solution and a saturated sodium hydrogen-carbonate solution. Separation of the organic phase and extraction of the aqueous phase with dichloromethane Ve twice. The organic phases were mixed and washed with a small amount of distilled ela. Then the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated using a vacuum rotary evaporator, and the concentrated concentrate was eluted on silica gel by lysing using a lysing mixture of a mixture of AD chloromethane 01010006108 and methanol at a ratio of .1:001 The main part was concentrated and treated with Ye ethyl acetate, and the compound named in the title crystallized during that in the form of a yellow solid. This precipitate was removed by vacuum filtration and dried until data on a constant weight in a vacuum drying oven at 0 0 a, resulting in 4.77 g of the compound named in the title (production rate - 597.7, the initial excess quantity > 780 by analysis). Me liquid chromatography using a Daicel Chiraleel column Melting point: 4-771 77 °C.

-01 3 4 Vda Sue JA Methyl-A; JET 43 (P-1; RA RY).

tetrahydrimidazole [VO] [=F OT naphthyridine

Ya

(7R.8R.9R)-2,3-Dimethyl-7.8-dihydroxy-9-phenyl-7.8.9.10-tetrahydroimidazo[1,2-h]{1,7]-naphthyridine —A=die SEY (84)-7; RA) suspension + g (18.07 mmol) of [7 OV] hydroimidazo [1"-H]-trans-01 A hydroxy-4-phenyl-N (8R,9R)- 2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-(V)tatheridinone oo

Se (initial excess > 7460) by liquid chromatography h[1,7]-naphthyridine-7-one performance using a Daicel Chiralcel column in 60 ml of methanol and the resulting suspension was cooled to temperature from ao to 0°C in a bath of hil-cooled methanol and at this temperature add 1 4 g (0 mM (YY, EY) of sodium borohydride) borohydride by means of a spatula within half an hour (gas release was observed).After the completion of the addition, CE the mixture for an additional ten minutes and then concentrated in a rotary vacuum evaporator at a bath temperature of 50 C. The resulting oily concentrate was dissolved in distilled ele was extracted with chloroform three times, the organic phases were mixed and washed with a small amount of water, then Gf da was filtered with sodium sulfate as J using an anhydrous 3 S55 vacuum evaporator and filtered. sodium sulfate 00 covalently with acetone tacetone, and the compound named in the title crystallized in the meantime, and the precipitate was removed by filtration, and das acetone was washed until dala at a constant weight at 0 m in a vacuum drying oven, resulting in 5.15 g of the compound named in the title in the form of a substance Crystalline dene, melting point ranges from 704-7036°C (GAOT rate = z) © Initial excess quantity > 460 by high-performance liquid chromatography using a Daicel Chiralcel column. -01 4 4 hydroxy-4-wick-a EEA (_-4p)-7; ©-dimethyl-7a; RA SV) LAY naphthyridine. [VN] 7-h] OV] tetrahydrimidazo (7S.8R.9R)-2,3-dimethyl-7.8-dihydroxy-9- phenyl-7.8.9, 1 0-tetrahydroimidazo[1,2- h][1,7]naphthyridine Yo then Yin gm of the mother liquor of example 11 on a silica gel by elution using a elution mixture of ethyl acetate A©/methanol in a proportion of 1 [V4] produced “Ao

0 gm of the named compound in the title in the form of oil that crystallizes when ethyl acetate is added. Its melting point ranges from 001-344. (ethyl acetate RA). [VN] [oY] naphthyridine. (8R.9R)-3-formyl-8-hydroxy-2-methyl-7-0x0-9-phenyl-7.8.9,10-tetrahydroimidazo[1,2-°h][1,7]naphthyridine 1 g of (RA) 89)-4-hydroxy-7; 7-dimethyl-71-oxo-4-phenyl-No A 9 110-tetrahydrimidazo [ [V OV] [ZY 0 naphthyridine (8R,9R)-8-hydroxy-2,3 - dimethyl-7-0x0-9-pheny!-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine in 0 mL of chloroform Dry and add © a gram of potassium permanganate, which was made by their owners. After the reaction mixture was stirred at room temperature for 56 days, the solid (sald) was removed by filtration. The filtrate was absorbed twice on a silica gel by elution using a elution mixture of dichloromethane J siliue/chloromethane at a ratio of 1/117, resulting in 01 g of the compound named in the title in the form of a semi-solid. D(RA(RY) .1#23)-7-hydroxymethyl-7-SUA hydroxy-7-methyl-1-phenyl-fA 10-tetrahydrimidazo [ [VO] [FY 10 Nephtheridin. (7R.8R,9R)-3-hydroxymethyl-7,8-dihydroxy-2-methyl-9-phenyl-7.8,9.10- tetrahydroimidazo[1,2-h][1,7]naphthyridine filament 0.07 g of RA (85)-7-formyl-4-hydroxy-1-Ue T=exo=A UA Yd 0 10-tetrahydrimidazo [ ) 7H] [VV] naphthyridine (8R,9R)-3-formyl- 8-hydroxy-2-methyl-7-0x0-9-phenyl-7,8,9,10-tetrahydroimidazo[ 1,2,1 , 7]naphthyridine in ¾ mL of dry methanol; Then 1 gm of sodium borohydride was added and the mixture was stirred for 700 minutes and concentrated in a vacuum. The oily concentrate was distributed between water and chloroform, then the organic layer was separated and dried over anhydrous sodium sulfate vo and concentrated. The resulting product was purified by flash chromatography on a silica gel by denaturation using a denaturing mixture of (SLB 10M chloromethane).

methanol J sitie/dichloromethane in a ratio of 1/4 yielded 0.8 g of the compound named in the title in the form of a semi-solid. Free name “CD3OH) 400 MHz) = U 1,4 (P HY 7-TAL) TAY (50 G 4,4 MHz = Av = AY is HY heated) 5 (G48 4 H) “H-4 HY 77/4 0 (P) Wide; z = 10 1,4 hen (HT HY unless)<—««(Ph—1 HY) this is for (z = z, no mocking V,VV ¢(Ph=4 HY) (g = %, 0 = 1 , no (H=2 HY V=(RY RA SY) . 05 +-7-deoxyisopropyllidene; SEY methyl-4-phenylene bark AA eb) hydroimidazo [VON [mY] naphthyridine (7S.8R,9R)-7,8-isopropylidenedioxy-2.3-dimethyl-9-phenyl-7,8.9,10-tetrahydroimidazo( 1,2-1) h[1,7]naphthyridine Dissolve 7 g of RA SY (4p8)-7;7-dimethyl-a;mS gm SEA -4—phenyl-/a cA 3 10-tetrahydro imidazo [ )© 7-h] OV] 7] naphthyridine (TS8RIR)-2,3- dimethyl-7,8-dihydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[ 1, 2-h[I, 7]naphthyridine in ve # ml of dry acetone and 10 ml of dry J tia ENN formamide N,N-dimethylformamide, then YY methoxy was added Propane 2,2-dimethoxypropane (by 01 de) and p-toluenesulfonic acid monohydrate (by 0 (pe) A) Then the mixture was stirred for 10 hours at dan temperature the room. Then distribute the _ reaction mixture between water and dichloromethane 00 pg 0100100. The organic layer was separated, washed with water, and then dried over anhydrous sodium sulfate. After evaporation of the solvent; The ore was impregnated on a silica gel by elution using a mixture (J goad) of ethyl acetate/methanol at a ratio of 0, resulting in 1.7 g of the named compound in the title in the form of colorless needles. ld melting point of 7-71 "m (dissolves; diethyl ether Jul .ve primary compounds a. SEY oY methyl-1-(7-phenyl-1-oxo-7) -propenyl)-+-bivaloyl amino imidazo O”-a]pyridine YAO

2,3-dimethyl-7-(3-phenyl-1-0x0-2-propenyl)-8-pivaloylaminoimidazo[1,2-a]pyridine Method A EY ( butyl LET (X= ait methyl-+-bivaloylaminoimidazo) [11;7-a]pyridine 7-tributylstannyl-2,3-dimethyl-8-pivaloylaminoimidazo{ 1,2-a]pyridine treated with a solution of 1 g of JEFF methyl-8-bivaloylaminoimidazo OO] ?-a]pyridine 2,3-dimethyl-8-pivaloylaminoimidazo[1,2-a]pyridine in 560 mL of diethyl ether by adding A mL of di-butyl lithium solution t-butyllithium with a concentration of 1.0 mole in p-pentane n-pentane (p denotes (gale point by point) at a hydrolyte. The mixture was stirred for 0 minutes and then treated with 7.7 ml of tri-chloride p_-butyltin, tri-n-butyltin chloride, 0, then the internal temperature was left to rise to room temperature, the mixture was poured on le water, and ethyl acetate was extracted three times, and the extracts were washed after mixing them with an amount of A little bit of water (Cling) over potassium carbonate, remove the solvent in vacuo, and absorb the resulting oil on a silica gel by lye using a mixture of ls ethyl acetate (Vi) duh petroleum ether 0 as the lye mixture Vintage ,01 g of SEY butyl SEY Y= Jit methyl-<*+-bivaloyl amino imidazo [OV] 7-a]pyridine T-tributylstannyl-2,3- dimethyl-8- pivaloylaminoimidazo[1,2-a]pyridine as viscous oil. b) 1 7-dimethyl-7-(*-phenyl-1-exo-7-propenyl)-+-bivaloyl aminoimidazo [oY]"-a]pyridine 2,3-dimethyl-7 -(3-phenyl-1-oxo0-2-propenyl)-8-pivaloylaminoimidazo[1,2-alpyridine 0

Js lis Amie JET (Yat 7-tributyl 1 gm) was treated with a solution of 7-tributylstannyl-2,3-dimethyl-8-pivaloylaminoimidazo[1,2-pyridine [=Y 3] amino imidase sequentially with 885 mg of tetrahydrofuran in 5 ml of alpyridine tetrahydrofuran (acetonitrile) SB, then with 0 mg of lithium chloride of cinnamoyl chloride parle 740. Then with bis(acetonitrile)palladium(I)chloride 0 palladium Ye mm for three hours, and the striking precipitate 0 palladium ““” was removed, and the mixture was stirred at chloride to yellow by vacuum filtration after cooling to the degree of acidity and washing with a small amount From 1 pm

YY

After drying in diethyl ether and tetrahydrofuran diethyl ether, 770 mg of the compound named in the title was produced in the form of hydrochloride salt, cel A, with a melting point ranging from 757-7769 °C (dissolving). ?-propenyl)-+-bivaloyl-iscorde-1-linf-7(-7-lithium SUEY 7a)0 pyridine [YO] amino imidazo 2,3-dimethyl-7- (3-phenyl-1-hydroxy-2-propenyl)-8-pivaloylaminoimidazo[1,2-a]pyridine with a density of 1 lb of +-bivaloylaminoimidazo-?; #- Dimethylimidazo Cilia solution was treated with the addition of 8-pivaloylamino-2,3-dimethylimidazo[1,2-a]pyridine?-a]pyridine OV] imidazo commercially available with a concentration of 1,0 molecular in t-butyllithium mL of te-butyllithium solution ??1 00 buffer so that no argon atmosphere bp YAS point by point at n-pentane an additional minute; Add 11 and after stirring at -/- for a period of a Vem, the temperature exceeds ethyl ether AB in © ml of cinnamaldehyde, 11 g of cinnamaldehyde, and then leave the mixture to warm (a VA = dry drop by drop (internal temperature lower than diethyl ether) and extracted three times by total amount of ml Fe to room temperature and carefully pouring over 1 water and washing the reddish organic phase ethyl acetate ml of ethyl acetate Ove neutralized and the solvent was removed in vacuo. sodium sulfate was dried over sodium sulfate data with wet water: 4. Se ether (J) ether was removed and the remaining yellowish suspension was treated with -1-Linv -?(-17-lithium SUEY OY 1 g of aspirated crystals yielding 2,3-dimethyl-7-(3-7-a]pyridine O-hydroxy-7-propenyl)-” Bivaloylaminoimidazo 0-0 whose grade ranges from phenyl-1-hydroxy-2-propenyl)-8-pivaloylaminoimidazo[ 1,2-a]pyridine 2140-14 from its fusion of aminoimidazo to oleolafib-4-(linipurb) -7-osca-1-lenf-*(-7-lithem SET 1b) pyridine [FY] 2,3-dimethyl-7-(3-phenyl-1-oxo-2-propenyl)- 8-pivaloylaminoimidazo[1,2-8[pyridine Yo

VS sae mu) = V= ie 7-di-Ye A solution of 0.0 ¥ g 2,3-dimethyl-7-(3-phenyl-1-hydroxy-pyridine [=Y 3]) was treated. propynyl)-8-bivaloyl amino imidazo

YY

in 00 ml of trichloromethane (2-propenyl)-8-pivaloylaminoimidazo[1,2-a]pyridine and stirred vigorously at 10 g manganese dioxide trichloromethane 1 h. Then the mixture was filtered and the filtrate was concentrated to dryness at room temperature (Jo) for (J) diisopropyl ether (Isopropyl) Ab in vacuum, and the resulting oil was treated with a small amount of 20.5 grams of the named compound, and the resulting crystals were removed from this process By aspiration filtration vintage 1 M. 01-0118 in the heading whose melting point ranges from “-dimethyl Y= gid glia Aig pr Y= sui) (di) JY) VY b. 7-a [pyridine A] imidazo 7-[3-(2-chlorophenyl)-1-oxo0-2-propenyl]-8-pivaloylamino-2,3-dimethylimidazo[ 1.,2- ajpyridine Ye

YO Obtain the named compound in the title whose melting point ranges from, by the same method used to prepare the example compound, hydrochloride in the form of M0 hydrochloride, 2-chlorocinnamoyl chloride A, method A, by the corresponding reaction with 1"-chlorocinnamoyl chloride 1 (production rate- ?

Y= gid leolafib-+-]linipurb-7-osca-1-(linfurolic_enanth-+_;eff2)-©[-7 c.ve pyridine [YO]imidazo Jie binary 7- [3-(2,6-dichlorophenyl)-1-0x0-2-propenyl]-8-pivaloylamino-2,3-dimethylimidazo[1,2- a]pyridine -718 contains the compound named in the title whose melting point ranges from dea ts using the same method used to prepare the compound hydrochloride 7195m in the form of hydrochloride TY. Chlorocinnamoyl SET with chloride 7- Jad by reaction of example A method (1.0) = z NY (rate 2 6-dichlorocinnamoy chloride

SUEY Y= gad leolafib-4-]lineporp-7-osca-1-)lenv d. 7-[7-(1-trifluoromethyl 7-a]pyridine QO] imidazo Ji 7-[3-(2-trifluoromethylphenyl)- 1-0x0-2-propenyl]-8-pivaloylamino-2,3- dimethylimidazo[1,2- Ye a]pyridine

Ye

YN on the named compound in the title whose melting point ranges from Ja a by the same method used to prepare the hydrochloride compound 04M in the form of hydrochloride by the corresponding reaction with 7-trifluoromethylcinnamoyl chloride of example A method. (7) VY = z (modified 2-trifluoromethylcinnamoyl chloride amino Jada A—(dus pr Jo and sca-1-escop-“ “-dimethyl-7-) ; Yao pyridine [EY OT imidazo] 2,3-dimethyl-7-(2,3-epoxy-1-0x0-3-phenylpropyl)-8-pivaloylaminoimidazo[1,2-a]pyridine -?-propenyl)-oska-1-linf-*( -7-Letham ET OY treated with a mixture of; 2,3-dimethyl-7-(3-phenyl-1-ox0-2-propenyl)-8-7-a]pyridine OV] imidazoe sid +-bivaloyl 0 mL of acetone 2661006 and 060 mg of 0 in pivaloylaminoimidazo[1,2-a]pyridine | 0 mL of water with the addition of 0.7 mL of peroxide 11 in sodium hydroxide Sodium hydroxide minute drop by drop with commercially available 01 aqueous hydrogen peroxide concentration +77 for a period of hydrogen peroxide hydrogen mix to degree Sy for an additional minute; At 1 gm of sodium thiosulfate 11 ml of water and 10 gestational yolks were treated with a mixture of, after phase separation, cthyl acetate 1 ml of ethyl acetate and 00 ml of sodium thiosulfate . ethyl acetate yo acetate; the aqueous phase was extracted by separation, the organic phases were mixed, washed with a small amount of water, and dried over carbonates in ial) and after removing the solvent in vacuo; He dried the oil, potassium carbonate, very empty, and it produced; g of the compound named in the title in the form of an amorphous mass. ‎-(1) nonnaporb-1-linf-"-nediliborbozia-0-“ a#-dimethyl-7-[(7+p8)- Lg >” Pyridine [FY A] aminoimidazo leulafib-+*-]ly-1 2,3-dimethyl-7-[(2S.3R)-2,3-O-isopropylidene-3-phenylpropane-1-on-1 -yl]-8-bivaloylaminoimidazo[1,2-a]pyridine methyl-+-bivaloylaminoimidazo JET 1 mol) of + YEO) g Te cud liter (I) liter 0 in 2,3-dimethyl-8-pivaloylaminoimidazo[1,2-a]pyridine [IY \] vo in anhydrous argon atmosphere with no moisture diethyl ether yu of diethyl 07 added ml 08 » needle and using a flexible needle 0. l o — and cool the mixture to 0

Yo

(+.7VY) mol) of a 1.0 molecular concentration of tert-butyllithium tert-butyllithium in p-pentane n-pentane point by point so that the temperature does not exceed -19°C during

Gaal BA ala) Minute. It forms a red suspension. After an additional 0 minutes are completed. Then slowly add one-third of the volume of Ve solution at -9 L for a period of time

.0 of VEO g of Y-(RY SY) 0-7-isopropylidene-?-phenylpropionate methyl (2S,3R)-2,3-O-isopropylidene-3-phenyl propionate (da all starting quantity: 744.00 by high-performance liquid chromatography using a Decyl Chiralcel Ano0 column) in 051 ml of THF dispensed drop by drop at a temperature below -6 °C within Yo minute. Then the remaining amount was quickly added drop by drop over five

0 minutes, the temperature rose to a Tem, and after the addition was completed; I remove the cooling bath. When the internal temperature reached -<70°C; 10 ml of methanol was added, and when the internal temperature reached zero degrees Celsius, 70010 ml of distilled water was added. Jad shal was separated in a separating funnel and the organic phase was washed five times with distilled water in an amount of 100 ml each time; Then the organic phase was extracted three times with acid

ve sulfuric sulfuric acid, its concentration is 701 by 100 ml in the first time and or ml in the other two times. The phases of sulfuric acid were mixed and treated with 7000 ml of SB dichloromethane and its pH was adjusted to 7 “, using a 01 M sodium hydroxide solution with cooling with ice and stirring vigorously. Separation of the organic phase. The aqueous phase was extracted with 010 mL of dichloromethane

.dichloromethane 0 and the dichloromethane phases were washed after mixing them twice with a small amount of distilled water. Then, the organic phase was anhydrous sodium persulfate, and the solvent was completely removed in vacuo, resulting in a brown oil that was treated with 00 ml of diethyl ether (A) elongation. After sowing, crystals were formed, which were separated by filtration after settling overnight and washed with diethyl ether. After drying in

ve emptiness OV, g of the named compound in the title was produced in the form of a pale yellow powder with a melting point of 8076 C (rate = z EV) 07.5 excess amount C 10 v1 starting > 749) by high-performance liquid chromatography using a column Daicel type Chiralcel Useful pharmacological properties Formula 1 compounds and their salts have pharmacological properties that make them suitable for commercial use. In particular, these compounds show clear inhibition activity 0 and have an excellent protective effect on gastric acid secretion to secrete gastric acid (stomach acid) and in particular cwarm-blooded animals stomach and intestines of warm-blooded animals Je selectiveness of the present invention by the effect of Lady compounds aa human.In this context; Particularly good, with no enteral activity effects, with a beneficial effect period, with clear intestinal efficacy, and with a wide therapeutic range. Gastric and intestinal protection, especially inflammatory gastrointestinal diseases, gastrointestinal diseases and pests 4 (such as gastric ulcers, gastrointestinal inflammatory diseases, cgastritis _ gastritis) “duodenal ulcers 4 piel BY! Stomach ulcers Vo functional infectious diseases related to excessive stomach acidity or taking medications that may be caused, for example, by organisms (hyperacidic or medicament-related functional gastropathy) Toxins (Helicobacter pylori) Microorganisms microorganisms anti-inflammatories amy Jw) medicaments medications bacterial toxins chemicals chemical compounds ¢ (antirheumatics and anti-rheumatics antiinflammatories | 00 stress gastric acid stomach acid 0 (ethanol (such as ethanol, its superiority, CPL, light of its excellent properties; the compounds according to the clear LE invention proved surprisingly well-known compounds from the previous technology in different models with antiulcerogenic properties in which the anti-ulcer properties were identified, and because With these properties, the compounds of formula 1 and their antisecretory properties 0 are approved as pharmacologically suitable for use in human and veterinary medicine, where

b used; In (ald) form for the treatment and/or prevention of stomach and/or intestinal disorders (intestine). Therefore, the invention also relates to compounds according to the invention for use in the treatment and/or prevention of the aforementioned diseases. o Similarly, the invention includes The use of compounds according to the invention to produce medicines for use in the treatment and/or prevention of the aforementioned diseases.In addition, the invention includes the use of compounds according to the invention for the treatment and/or prevention of the aforementioned diseases.The invention also relates to medicines containing one or more compounds © with the formula and/or their pharmaceutically approved salts The drugs are prepared by processes known by themselves and familiar to a person skilled in the technique The pharmacologically active compounds according to the invention (i.e. active compounds) are used as drugs either as such or preferably in combination with auxiliaries or appropriate pharmaceutical excipients in the form of tablets A “Ya” ccoated tablets V capsules “capsules” suppositories csuppositories patches (eg TTS) emulsions Suspensions or csolutions where it is desirable that the content of the active compound ranges from 1.1 to 798 and where; by appropriate selection of adjuvants and excipients; Pharmaceutical administration form (eg delayed-release or enteric form) can be achieved that perfectly matches the active compound and/or the times of onset of the desired effect. A person experienced in Ail shall be in the light of his/her knowledge Familiarize yourself with Jalal with the appropriate auxiliaries or excipients for desired pharmaceutical formulations In addition to solvents Jin cgel-forming agents suppository bases tablet auxiliaries 0 Active compound carriers (AY! active compound carries).

TA

Or, in particular, enhancers, colorants, colorants, csolubilizers 55M, dissolving agents (such as complexing agents and permeation promoters). Cyclodextrin or by injection orally. The active compounds can be administered orally percutaneously or parenterally through the skin. In general, it has been shown to be beneficial in human medicine to administer the active compound (or range from daily dose of the active compounds) if administered via Oral in a daily dose of 1.5 to 0.1, preferably from 05 to ©, especially from Te to about 1.01 in doses of body weight milligram/kilogram (mg/kg) mg/kg into; doses; if required to achieve outcome 1 single or multiple; preferably in the range of 0 (particularly in the case of desired parenteral treatment. In the case of parenteral treatment Injections generally use SA (intravenous administration oll intravenous administration of the active compounds and the optimal dose method of administration are similar or lower doses. The optimal dose of the active compounds necessary in each case can easily be determined by any experienced person In technology, depending on his knowledge experience. ve of the invention and/or its salts to treat aforementioned diseases. pharmacologically active constituent from Na) tranquilizers from another pharmacy. Examples of these components include painkillers, convulsions (diazepam, diazepam, Jie, cbenzodiazepines, a group of benzodiazepine compounds, antisecretory agents, camylofin, or bietamiverine (such as spasmolytics, fencarbamide, oxyphencyclimine). Oxycycline Jia) anticholinergics choline or tetracaine (such as tetracaine) local anesthetics local anesthetics ¢ (phencarbamide amino acids or amino acids vitamins vitamins enzymes and enzymes (procaine procaine) if ve

Lay And we have to emphasize in this regard in particular the use of a combination of compounds

Jie) 112 blockers 112 of the invention with pharmaceutical preparations that suppress acid secretion such as blockers 01M rq and inhibitors of the enzyme synthesis of adenosine triphosphate (ranitidine scimetidine, cimetidine 11/16) adenosine triphosphatase 11 6/ To transfer potassium and hydrogen ions, or with what is also called (pantoprazole, comeprazole (such as omeprazole ATPase) “pirenzepine Ja) peripheral anticholinergics with peripheral cholinesterase antagonists in order to increase the effect gastrin antagonists With anti-gastrin (telenzepine 0) than the basic Shad in an additional or excessive amount and / or eliminating or reducing side effects, or antibacterially active substances, the compounds are used in combination with effective substances against bacteria. penicillins ctetracyclines (such as cephalosporins 11:8105800:105 M©” tetracycline compounds or instead nitroimidazoles nitrolimidazoles cmacrolides macrolides ¢penicillins to reduce the effect of Helicobacter pylori (bismuth salts including bismuth salts) 0 We can mention examples of combined active ingredients against bacteria Helicobacter pylori Cephaloin camoxyeillin Amoxicillin <ampicillin Ampicillin 006210611110 Ampicillin Cefotaxime 010<106]; imipenem 100106060 gentamicin cefoxitin cefoxitin ccefalothin ciprofloxacin cerythromycin erythromycin amikacin amikacin gentamycin azithromycin cclarithromycin metronidazole 080001002016 ciprofloxacin Ve + clarithromycin and combinations Of which (such as a combination of clarithromycin, azithromycin. (metronidazole, metronidazole) Pharmacology J Bl Gal) Effect The excellent gastric acid protective effect and the stimulating effect of gastric acid secretion of the compounds according to the invention can be demonstrated in experimental animal models. The numbers of these compounds correspond to the Lag mentioned in the examples

Testing of the secretion- 439 All (ama dja) inhibiting action on the perfused rat stomach daa pentagastrin-stimulated acid secretion intravenous administration in vivo after intravenous administration perfused rat stomach 10 minutes

Table A No. of compound Z (µmol/kg K16/m.m.) 0 cg A Method ° Abdominoplasty anesthetized rats (female rat type 60 weighing 06-70 g; given PE L/P 0,* # Of urethane intramuscular (i.m.) after tracheotomy in the root of the incision of the median upper abdomen, and a polyvinyl chloride (PVC) catheter fixed Through the mouth into the esophagus 85 and another OLE 0 fixed through the pylorus so that both ends of the tube protrude into the gastric lumen directly. through a .side opening and after flushing Tam (amount of about 100-*1 ml); Je continuously warm physiological NaCl solution at 77 °C through the stomach (rate © ml/min; at a pH of 1 ranging from 5-7.8, from Brown-Unita 1 1 Hana-Q: 3, by determining the pH (with a pH meter No. 677 632 pH meter using a glass electrode electrode type 147 (EA = © mm; From Metrohm and titrated with 1 solution of 100M Bas to pH 17 (type 110 665 Dosimat from Metrom 1460010); the secreted amounts of HCI were determined © In the effluent liquid in all Alls collected in it at a time period of 115 minutes.

Gastric acid secretion was stimulated by an infusion of 1 microgram/kilogram (um/kg) (milliliter/hour (ml/h) of pentagastrin). A continuous infusion (into the left femoral vein) about 0 minutes after the end of the operation (i.e. after determining the primary CB). © And I was given dad_ to be tested intravenously with volumes Jl equal to 1 milliliter/kilogram (ml/kg) after +1 488 from the start of a continuous pentagastrin infusion.

The body temperature of the animals was kept at a constant temperature ranging from A to M with infrared irradiation and using heat pads 0 (automatic, stepless control using a thermal probe via

. (rectal temperature sensor) 01 m

Claims (1)

Claims 1-1 is a compound of the formula ]: R3 R2 R4b = N R5a NH 0) 85 = R7 v where R1 ¢ is 1-4C-alkyl C,—Cy— JH R2 5 represents an alkyl-©-© 1-4C-alkyl or hydroxy-alkyl-0- chydroxy-1-4C-alkyl R3 1 represents a hydrogen atom or A halogen, one of the alternatives 848 and 846 represents 5.0 hydrogen, and the other alternative represents 5.0 A chydrogen hydroxyl ¢1-4C-alkoxy Ci Cy nS 5S < hydroxyl 9 alkoxy-, 0-,©-alkoxy 0,70 C=C JK ¢1-4C-alkoxy-1-4C-alkoxy 1-carbonyloxy ¢1-4C-alkylcarbonyloxy or where J Sy 846 and Las R4b is an 11-coxygen atom (Jia VY), one of the alternatives 858 and 1850 is a hydrogen atom, and the other alternative represents a vr hydrogen atom, chydrogen, hydroxyl alkoxy-T- c1-4C-alkoxy Ve alkoxy-b©-,©-alkoxy-.0-© 1-4C-alkoxy-1-4C-alkoxy or alkyl-0-0 carbonyloxy “1-4C-alkylcarbonyloxy” or where RSa J— Siu and Lae RSb 5,0 1 oxygen 01 VY or where 1 represents substituents 848 and 845 on the one hand and substituents 858 and 856 on the other in each and alls hydrogen atom JT Sig hydrogen for the other two substitutes in every 10m 1:31 Y. Lae case (-O-CH,-0-) methylenedioxy radical or YA ethylenedioxy radical ¢(-0-CH,-CH,-O-) ethylenedioxy YY where RSa radicals “Rb Rda and RSb do not represent at the same time by) hydrogen “hydrogen YY Y¢ 6 represents a hydrogen atom chydrogen a halogen of alkyl-n-n” 1 -4C-alkyl Yo alkoxy-- dais SCC Ss SU (1-4C-alkoxy amino ¢1-4C-alkoxycarbonylamino 71 alkoxy-©-,0-alkoxy--carbonyl l-amino 1-4C -alkoxy-1 -4C-alkoxycarbonylamino or trifluoromethyl Jia 7 YA (35 hydrogen) ("p0:08:" ¢halogen alkyl-net-© 1-4C-alkyl or Ya alkoxy ,0-0 ¢1-4C-alkoxy v. or salts of this compound. 0 ?- the compound of formula 1 according to the claim) 0 where | ¢1-4C-alkyl C,—C,— J is 1 Y hydroxy-1-4C-alkyl C,;~Cy=Jili= or hydroxy 1-4C-alkyl C,—C,— ISH R2 r hydrogen represents a hydrogen atom, Jia 3 ¢, and one of the two substituents represents Rda and 1845 300 hydrogen, and the other substituent represents the “1-4C-alkoxy alkoxy-,0-© hydroxyl” atom. Hydroxyl chydrogen hydrogen 1 oxygen an oxygen atom Las R4b or where 4 and y cleaves A and one of the alternatives 1858 and 8506 represents a hydrogen atom and the alternative (DAY) represents a 9 hydrogen atom chydrogen hydroxyl or 1-4C-alkoxy C= Cy nS 5S] or 01 where RSa Jr Si and M85 Las coxygen 11 where the radicals do not represent RSa «R4b Rda and RSb at the same time) 3 hydrogen <hydrogen VY Jhe or trifluoro halogen a hydrogen atom 0970:0860 halogen (Jia 6 VY trifluoromethyl Ve chalogen or halogen hydrogen representing a hydrogen atom 7 Vo Y vA tt 1 or the salts of this compound. 1 *- the compound according to claim 1a with the formula *1: Ra 82 ago 843 Réd NS N Re NH {I wf) v Xm 87 3 where 1 1 Represents alkyl-n-h “1-4C-alkyl R2 5 represents 1-4C-alkyl C=C JS or hydroxy-1-4C-alkyl 0- hydroxy-1-4C-alkyl 1 3 represents an atom Hydrogen v, one of the two substituents, Ria and Reb, represents 303 hydrogen, and the other substituent represents the A hydro chydrogen atom (ma hydroxyl ¢1-4C-alkoxy C= Cy nS 5S) hydroxyl 9 One of the two substituents, RSa and RSb, represents a hydrogen atom, and the other substitution represents a 10 chydrogen atom (hydroxyl or 1-4C-alkoxy C= Cy nS 5S). Cua 1 does not represent radicals and 84 “R4b 858 and RSb at the same time) 3 hydrogen <hydrogen VY VY 6 represents) 3,5 hydrogen hydrogen halogen or trifluoromethyl Ve and R7 Vo represent a hydrogen atom (chalogen 5) or salts of this compound. 0;4- the compound of the formula *1 according to claim F . where RI v is the 0-©-,0-alkyl ¢1-4C-alkyl M R2 ¢ represents 1-4C-alkyl C,—C,— Jt or hydroxymethyl Jia R3 ° hydrogen atom Jia Rda 1 hydrogen atom hydrogen v 46 represents hydroxyl or ¢1-4C-alkoxy C;=Cy= L&I A 48 represents a hydrogen atom hydroxyl or C=C nS SI ¢«1-4C-alkoxy 9 yo 0 represents a hydrogen atom Jia 6 VA a hydrogen atom halogen or trifluoromethyl 11 and VY 7 represents a hydrogen atom or halogen chalogen Vi or salts of this compound. 1 0— compound of the form *[ according to the claim?; Cua Y 1 represents ¢1-4C-alkyl C,—C,— J) R2 v represents ¢1-4C-alkyl C,—C,— JH Jia R3 ¢ atom Hydrogen 5 426 represents a hydrogen atom R4b 1 represents hydroxyl L 42 represents hydroxyl A 506 represents a hydrogen atom chydrogen 9 6 represents a hydrogen atom halogen halogen or trifluoromethy! 01 and 1 7 represent the hydrogen atom or halogen VY and the 5 salts of this compound. 1 = the compound of claim 1; chosen from the group consisting of: Y not 7-hydroxy AEA; Yd adie SUEY 8 4 10-tetrahydro Ao + \ 7,8-dihydroxy-2,3-dimethyl-9-phenyl-nevipyridine [1 1 7-h] A] imidazo 1 <7,8,9,10-tetrahydroimidazo[ 1,2-h [1,7]naphthyridine ¢ A] hydroimidazo trans-01 A-dimethyl-4-phenyl-A CY ° 2,3-dimethyl-9-phenyl-7,8,9,10- tetrahydroimidazo[1,2-(V)naphthyridinone]70["-h]4 <h][1,7]naphthyridin-7-one L A] hydroimidazo trans-01 dA 4-(7-chlorophenyl)-7;7-dimethyl-7a;A 9-(2-chlorophenyl)-2,3-dimethyl-7,8,9,10-(V)taphthyridinone [VO] "-h]4 stetrahydroimidazo[1,2h][1,7]naphthyridin-7-one 01 methyl-a; +8 9; 10-Tetrahydro SEY chlorophenyl)-; SET 4-(7;1 9-(2,6-dichlorophenyl)-2,3-dimethyl-(V) naphtheridinone [7 0]' -h] NV] imidazo VY +7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one yy hydro-trans-trans-01 A 4-( 7-trifluoromethylphenyl)-7;7-dimethyl-7;) ¢ 9-(2-trifluoromethylphenyl)-2,3-dimethyl- (Vv) naphtheridinone [Vey] [= A] imidazo Vo «7,8,9,10-tetrahydroimidazo[ 1,2-h][ 1,7]naphthyridin-7-one O] hydroimidazo trans-10 dA methyl-4-phenyl- /A JET 7-hydroxy-A 7-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10- Cp phd) [v VN] [-— Y VA stetrahydroimidazo[1, 2-h[1,7]naphthyridine v4 methyl-/a;4 4;10-tetrahydro SUEY;7-iscordia-17-(lenv)4-(7-chloro9 9-(2-chlorophenyl) )-7-hydroxy-2,3-dimethyl-nephridine [7 »0[ 7-H] A] imidazo 1 «7,8,9,10-tetrahydroimidazo] |L-1,2 ‎ 1,7 |naphthyridine YY -101 4A Vd oY ;7-iscordia-1/-)lenv "7-dichloro 7-4 yy 9-(2,6-dichlorophenyl)-7-hydroxy- naphthyridine [V ¢V] [=F A] tetrahydroimidazo Y¢ «2,3-dimethyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine Yo -01 3 in Vd he SUEY Ym oS padi 4-(7-trifluoromethyl 7 9-(2-trifluoromethylphenyl)-7- naphthyridine [VO] 7-h] A] tetrahydrimidazo vy <hydroxy- 2,3-dimethyl-7,8,9,10-tetrahydroimidazo[ 1,2-h)[ 1,7]naphthyridine YA hydroimidazo trans-01 9 A + “-hydroxy-?; #-dimethyl-4-phenyl-7 re 01 pm 8-hydroxy-2,3-dimethyl-9-pheny!-7,8,9,10- (V) naphtheridinone [VY] “-h] AV] v. ctetrahydroimidazo[1,2-h} [1,7] naphthyridin-7-one 79 AA Voda Spa SWFA Yd SEY (Sy) ry (78,8R,9R)-2,3-Dimethyl-naphthyridine [VO] [=F OV] hydroimidazo trans-0 ry ¢ 7,8-dihydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7)naphthyridine ve -01 3 P Vim Rsca-17- (84)-7-Formyl-/-hydroxy-7'-methyl RA) Yo (8R,9R)-3-Formyl-8-hydroxy-2-naphthyridine [VV] 7-h] oN] tetrahydroimidazo 7 ¢methyl-7-0x0-9-phenyl-7,8,9,10-tetrahydroimidazo( 1,2-h][1,7) naphthyridine vy hydroxy-7-methyl-phenyl-la SEA (81)-"-hydroxymethyl-; (RA RY) 2 (TR,8RIR)-3-naphthyridine [V OV] [= OV] Hydroimidazo Trans-01 4 A ra Hydroxymethyl-7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo [ 1,2- ¢ h][1,7]naphthyridine 1 f SV) 3 (HgL-45p)-A +-7-dioxy-isopropyllidene; SLE methyl-4-phenyl-E od eA er 10-tetrahydrimidazo [OV] 7-H] [VV] naphthyridine (7S.8RIR)-T,8- Isopropylidenedioxy- 2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-4] 6 h][1,7] naphthyridine M £1 or the salt of this compound. 01 7- The compound according to Claim 6 in the form OR configuration or salt thereof. =A The compound according to claim 1 has the chemical name “Y=(R? RA (RY) Y 4-dihydroxy-?; (SUEY methyl-4-phenyl-/ E6 4 10-tetrahydro ¥ imidazo [VV] [=Y OO] naphthyridine (7R,8R,9R)-7,8-dihydroxy-2,3-dimethyl-9- “phenyl-7 ,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine ¢ ° or salt from it. 4- A medicine that includes the Lay compound of claimant 1 and/or its salt 01 pm Y pharmacologically tolerable salt with auxiliaries and/or 1 excipients .customary pharmaceutical 01-1 Use of compounds according to claim 1 and their pharmacies pharmacologically tolerable salts Y to produce medicines for the prevention and treatment of gastrointestinal diseases. 1 AO